Doyonnas Regis, Nielsen Julie S, Chelliah Shierley, Drew Erin, Hara Takahiko, Miyajima Atsushi, McNagny Kelly M
The Biomedical Research Centre, University of British Columbia, 2222 Health Sciences Mall, Vancouver, Canada V6T 1Z3.
Blood. 2005 Jun 1;105(11):4170-8. doi: 10.1182/blood-2004-10-4077. Epub 2005 Feb 8.
Podocalyxin/podocalyxin-like protein 1 [PCLP1]/thrombomucin/MEP21 is a CD34-related sialomucin. We have performed a detailed analysis of its expression during murine development and assessed its utility as a marker of hematopoietic stem cells (HSCs) and their more differentiated progeny. We find that podocalyxin is highly expressed by the first primitive hematopoietic progenitors and nucleated red blood cells to form in the embryonic yolk sac. Likewise, podocalyxin is expressed by definitive multilineage hematopoietic progenitors and erythroid precursors in fetal liver. The level of podocalyxin expression gradually declines with further embryo maturation and reaches near-background levels at birth. This is followed by a postnatal burst of expression that correlates with the seeding of new hematopoietic progenitors to the spleen and bone marrow. Shortly thereafter, podocalyxin expression gradually declines, and by 4 weeks postpartum it is restricted to a rare population of Sca-1(+), c-kit(+), lineage marker(-) (Lin(-)) cells in the bone marrow. These rare podocalyxin-expressing cells are capable of serially reconstituting myeloid and lymphoid lineages in lethally irradiated recipients, suggesting they have HSC activity. In summary, we find that podocalyxin is a marker of embryonic HSCs and erythroid cells and of adult HSCs and that it may be a valuable marker for the purification of these cells for transplantation.
多配体蛋白聚糖/多配体蛋白聚糖样蛋白1 [PCLP1]/血栓黏蛋白/MEP21是一种与CD34相关的唾液酸黏蛋白。我们对其在小鼠发育过程中的表达进行了详细分析,并评估了它作为造血干细胞(HSC)及其更分化后代标志物的效用。我们发现,多配体蛋白聚糖在胚胎卵黄囊中最早形成的原始造血祖细胞和成核红细胞中高度表达。同样,多配体蛋白聚糖在胎肝中的定型多谱系造血祖细胞和红系前体细胞中表达。随着胚胎进一步成熟,多配体蛋白聚糖的表达水平逐渐下降,在出生时达到接近背景水平。随后在出生后出现表达激增,这与新的造血祖细胞在脾脏和骨髓中的定植相关。此后不久,多配体蛋白聚糖的表达逐渐下降,到产后4周时,它仅限于骨髓中罕见的一群Sca-1(+)、c-kit(+)、谱系标志物阴性(Lin(-))细胞。这些罕见的表达多配体蛋白聚糖的细胞能够在接受致死性照射的受体中连续重建造血髓系和淋巴系,表明它们具有造血干细胞活性。总之,我们发现多配体蛋白聚糖是胚胎造血干细胞和红细胞以及成体造血干细胞的标志物,并且它可能是用于移植而纯化这些细胞的有价值的标志物。